The invention provides a pharmaceutical composition for treating depression and a preparation method and application thereof. The pharmaceutical composition comprises the active pharmaceutical ingredients, by weight, 80-150 parts of rhizoma cyperi, 80-150 parts of cardamom, 80-150 parts of mint, 80-120 parts of fennel, 60-100 parts of radix bupleuri, 30-80 parts of selfheal, 80-120 parts of humifuse euphorbia herb, 120-200 parts of liquorice, 100-150 parts of Chinese date, 50-100 parts of spina date seed, 30-50 parts of cortex albiziae and 60-100 parts of myrobalan. A rat chronic mild unpredictable stress model, a rat olfactory bulb excision model, a mouse behavior despiring model and a 5-hydroxytryptophan induced mouse head shaking behavior model prove that the pharmaceutical compositionhas an anti-depression effect, in addition, the pharmaceutical composition can be prepared into tablets, pills, granules, syrups and capsules through a conventional method, and the preparation methodis simple, safe, economical and effective.